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Tofogliflozin decreases body fat mass and improves peripheral insulin resistance

Ren Matsuba1, Ikuro Matsuba2, Mototsugu Shimokawa3

  • 1Department of Internal Medicine, Division of Metabolism and Endocrinology, St Marianna University School of Medicine, Kanagawa, Japan.

Diabetes, Obesity & Metabolism
|January 10, 2018
PubMed

Insights

Tofogliflozin, a sodium-glucose co-transporter-2 inhibitor, significantly improved insulin sensitivity and glucose uptake in type 2 diabetes patients. These benefits were linked to a reduction in body fat mass after 12 weeks of treatment.

Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by insulin resistance and impaired glucose metabolism.
  • Sodium-glucose co-transporter-2 (SGLT2) inhibitors represent a therapeutic class that enhances glucose excretion, potentially impacting systemic glucose handling.
  • Understanding the specific effects of SGLT2 inhibitors on peripheral glucose uptake is crucial for optimizing T2DM management.

Purpose of the Study:

  • To evaluate the impact of tofogliflozin, an SGLT2 inhibitor, on peripheral glucose uptake in patients with T2DM.
  • To assess changes in body composition, glucose metabolism, and other metabolic parameters following 12 weeks of tofogliflozin treatment.
  • To investigate the correlation between improvements in glucose uptake and changes in body fat mass.

Main Methods:

  • A single-arm, open-label study involving 16 patients with T2DM receiving dipeptidyl peptidase-4 inhibitor therapy.
  • Peripheral glucose uptake was measured using the hyperinsulinaemic-euglycaemic clamp technique (assessing M value and M/I ratio).
  • Key variables including body weight, blood pressure, glucose metabolism, liver function, lipid profile, and body composition were monitored before and after 12 weeks of tofogliflozin administration.

Main Results:

  • Tofogliflozin treatment for 12 weeks resulted in significant reductions in glycated haemoglobin, body weight, body fat mass, and lean body mass (P < .001).
  • Peripheral glucose uptake, a marker of insulin sensitivity, significantly increased (M value by 0.90, M/I ratio by 0.49; both P < .05).
  • The improvement in the M value was significantly correlated with the reduction in body fat mass (P < .05).

Conclusions:

  • Tofogliflozin effectively enhances insulin sensitivity and peripheral glucose uptake in patients with T2DM.
  • The observed improvements in glucose metabolism are significantly associated with a decrease in body fat mass.
  • These findings highlight a potential mechanism by which SGLT2 inhibition may benefit T2DM management beyond glycemic control.
Keywords:
DPP-4 inhibitorbody compositioninsulin resistancetype 2 diabetes

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